Genetic Variant ITPRID1:p.Ala30Thr (chr7-31553112-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001257967.3(ITPRID1):c.88G>A(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000655 in 1,601,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A30V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ITPRID1
NM_001257967.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Publications

3 publications found

Variant links:

Genes affected

ITPRID1 (HGNC:27363): (ITPR interacting domain containing 1) Predicted to enable signaling receptor binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ITPRID1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06987202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRID1	NM_001257967.3	MANE Select	c.88G>A	p.Ala30Thr	missense	Exon 3 of 15	NP_001244896.2	Q6ZRS4-1
ITPRID1	NM_194300.5		c.88G>A	p.Ala30Thr	missense	Exon 2 of 14	NP_919276.2	Q6ZRS4-1
ITPRID1	NM_001257968.3		c.88G>A	p.Ala30Thr	missense	Exon 2 of 15	NP_001244897.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRID1	ENST00000615280.5	TSL:2 MANE Select	c.88G>A	p.Ala30Thr	missense	Exon 3 of 15	ENSP00000478518.2	Q6ZRS4-1
ITPRID1	ENST00000407970.7	TSL:1	c.88G>A	p.Ala30Thr	missense	Exon 2 of 14	ENSP00000384416.3	Q6ZRS4-1
ITPRID1	ENST00000888409.1		c.88G>A	p.Ala30Thr	missense	Exon 2 of 14	ENSP00000558468.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000144

AC:

AN:

229082

AF XY:

0.000138

show subpopulations

Gnomad AFR exome

AF:

0.0000689

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000773

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000492

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000642

AC:

AN:

1449612

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

719732

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33264

American (AMR)

AF:

0.000162

AC:

AN:

43262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.000485

AC:

AN:

39148

South Asian (SAS)

AF:

0.000346

AC:

AN:

83906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52692

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1105742

Other (OTH)

AF:

0.0000667

AC:

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000775

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000449

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.63

M_CAP

Benign

0.025

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.10

Sift

Uncertain

0.013

Sift4G

Benign

0.082

Polyphen

0.82

Vest4

0.030

MVP

0.50

MPC

0.049

ClinPred

0.060

GERP RS

3.5

Varity_R

0.077

gMVP

0.11

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over